Malaria currently represents one of the most prevalent infections in tropical and subtropical areas throughout the world. Each year, malaria affects around 300 million people and kills 1 to 3 million people in developing countries. Malaria is caused by the mosquito-borne hematoprotozoan parasites belonging to the genus Plasmodium (P.). Malaria parasites have a life cycle consisting of several stages. Each one of these stages is able to induce specific immune responses against the corresponding stage-specific antigens. Malaria parasites are transmitted to man by several species of female Anopheles mosquitoes. Infected mosquitoes inject the sporozoite form of the malaria parasite into the mammalian bloodstream. Before invading hepatocytes, sporozoites remain for a few minutes in the circulation. At this stage the parasite is located in the extracellular environment and is exposed to antibody attack, mainly directed to the circumsporozoite (CS) protein, a major component of the sporozoite surface. Once in the liver, the parasites replicate and develop into schizonts (up to 20,000 per infected cell). During this intracellular stage of the parasite, the main effectors of the host immune response are T lymphocytes, especially CD8+ T cells. Ad35.CS.01 is a malaria vaccine for which a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen is inserted in a replication deficient Adenovirus 35 backbone. It is hypothesized that the Ad35.CS.01 vaccine will prevent the P. falciparum parasite, which causes malaria, from entering and developing within the liver of those who become infected. Ad35.CS.01 would therefore be expected to reduce malaria-attributable morbidity and mortality. The primary objective is to assess the safety and reactogenicity of 4 ascending dosages of Adenovirus Type 35 circumsporozoite malaria vaccine among healthy, semi-immune, subjects given in 3 doses at 0, 1 and 3 months by intramuscular (IM) injection. The secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based circumsporozoite malaria vaccine through performance of Humoral Immune Assays (ELISA [enzyme-linked immunosorbent assay] for antibodies to circumsporozoite antigen and Adenovirus Neutralization Assay for neutralizing antibodies to Adenovirus Type 35) and Cellular Immune Assays (Elispot and Flow Cytometry) for CS-specific CD4+ and CD8+ T cell responses and a whole blood ELISA assay to measure secreted cytokines. This is a phase I randomized, controlled, double-blinded, dosage-escalation trial to evaluate the immunogenicity, safety, and reactogenicity of an Adenovirus Type 35 based circumsporozoite malaria vaccine in Burkinabè, in semi-immune, healthy adults 18 to 45 years of age. Researchers propose to confirm the safety of each dosage of the new vaccine by assessing safety laboratory parameters and reactogenicity for 14 days after the initial dose in the lower dosages before escalating to the next dosage level. Each dosage level group will include 10 subjects given vaccine intramuscularly. Two subjects in each dosage group will receive normal saline as placebo control.